We have continued studies of the intracisternal A-particle (IAP) genes, a genetically distinctive type of retrovirus-like element or retrotransposon that is extensively reiterated in the genomes of mouse and other rodent species. The family of mouse IAP elements, about 1000 per haploid genome, including a number of structural variants with deletions and/or insertions at characteristic positions. Last year, we described a collaborative study with Drs. K. Moore and K. Ishizaka in which a cDNA clone encoding an IgE-binding factor (a form of T-cell-secreted IgE-regulatory protein) was identified as a member of the IAP gene family. We have since characterized 5 additional cDNA clones that code for IgE-binding factors. Each one proved to be a different structural variant of the full-length IAP proviral element. Antisera against the IAP core protein 73 reacted with the IgE-binding factors, and isolated p73 itself was shown to bind to IgE and to potentiate IgE production in immunized B-lymphocytes. Dr. Z. Grossman has isolated several cDNA clones from normal mouse thymus by immuno-selection for the production of proteins cross-reactive with p73. These clones are being compared with the IgE-binding factor clones by sequence analysis. J. Mietz has essentially completed the nucleotide sequencing of MIA14, a full-size 7.3 kb mouse IAP genomic element. In other IAP-related studies, Dr. A. Feenstra completed work showing that in vitro DNA methylations at a cluster of three HhaI sites in the 5' region of a cloned IAP LTR completely abolished the capacity of the LTR to promote CAT gene expression in an appropriately constructed recombinant plasmid; and that methylation at a single HpaII site very near the 3' end of the LTR reduced activity by 75%. These observations define a system for elucidating the mechanism by which methylation inhibits IAP and other retroviral expression. J. Fewell has identified as hnRNP proteins A1 and A2 the nuclear antigens that cross-react with an antiserum prepared against the IAP core protein p73. He has shown that these antigens can be markedly depleted under certain growth conditions and is examining the possibility that proteins A1 and A2 are produced in rate-limiting amounts in rapidly growing cells.